ObjectiveThis paper aims to investigate the effects and mechanism of Mimenghua prescription in modulating the mitogen-activated protein kinase kinase （MEK）/rat sarcoma viral oncogene homolog （Ras）/rapidly accelerated fibrosarcoma kinase （Raf）/extracellular signal-regulated kinase （ERK） signaling pathway to inhibit inflammatory responses in a dry eye animal model. MethodsA total of 60 C57BL/6J mice （eight weeks old， half male and half female） were used in the experiment. Ten mice were randomly selected as the blank control group， while the remaining 50 were exposed to a controlled dry system and received instillation of 0.2% benzalkonium chloride （BAC） into the eyes for four weeks to establish a dry eye mouse model. After successful modeling， the mice were randomly divided into five groups： Model group， sodium hyaluronate group， and Mimenghua prescription groups with low dose （4.83 g·kg^-1）， medium dose （9.67 g·kg^-1）， and high dose （19.34 g·kg^-1）. The mice in the model group received an equal volume of normal saline via gavage for four weeks. The mice in the sodium hyaluronate group received instillation of sodium hyaluronate eye drops twice daily for 14 consecutive days. The tear secretion volume， tear film break-up time （TBUT）， and corneal fluorescein staining were evaluated once every two weeks. After four weeks of administration， mice were euthanized， and their lacrimal gland tissues and corneas were harvested. Hematoxylin-eosin （HE） staining was used to assess histopathological morphology. Western blot was performed to detect the protein expression levels of MEK， Ras， Raf， and ERK. Enzyme-linked immunosorbent assay （ELISA） was used to measure the contents and expressions of MEK， Ras， Raf， ERK， and interleukin （IL）-1β in lacrimal gland and corneal tissues of the mice in each group. Quantitative real-time polymerase chain reaction （Real-time PCR） was employed to determine mRNA expression levels of MEK， Ras， Raf， and ERK. ResultsThe Mimenghua prescription groups and the sodium hyaluronate group exhibited significantly increased tear secretion volume （P<0.05） and prolonged TBUT （P<0.05） after treatment. Ocular surface damage of mice was visibly recovered. Western blot results indicated that protein expression levels of MEK， Ras， Raf， and ERK in the lacrimal gland and corneal tissues were significantly downregulated in the sodium hyaluronate group and Mimenghua prescription group with high dose （P<0.05）. ELISA results showed that IL-1β levels were highest in the model group but significantly reduced in the sodium hyaluronate group and Mimenghua prescription groups （P<0.05）. Both ELISA and Real-time PCR results demonstrated that the expression levels of MEK， Ras， Raf， and ERK in the lacrimal glands and corneal tissues were significantly elevated in the model group （P<0.05）， but markedly downregulated in the sodium hyaluronate group and Mimenghua prescription groups （P<0.05）， suggesting that Mimenghua prescription can decrease the expressions of MEK， Ras， Raf， and ERK in the lacrimal glands and corneal tissues. ConclusionMimenghua prescription can reduce inflammatory responses， increase tear secretion， prolong TBUT， and promote corneal recovery by inhibiting the MEK， Ras， Raf， and ERK signaling pathways in lacrimal gland and corneal tissues.

Background and Aims:Rhabdoid carcinoma of the colon(RCC)is an exceptionally rare and highly aggressive malignancy characterized by early metastasis and poor prognosis,with no standardized treatment available.We report a case of ascending colon RCC and summarize previously published cases to improve understanding of its clinicopathologic and molecular features.Methods:The clinical data,imaging,pathology,and immunohistochemistry of one patient treated at Xiangya Hospital were retrospectively analyzed.In addition,36 published RCC cases were systematically reviewed.Clinical characteristics,tumor location,immunophenotype,molecular alterations,treatments,and survival outcomes were extracted and summarized.Results:A 71-year-old man presented with abdominal distension,pain,and altered bowel habits.Imaging and colonoscopy indicated an obstructing ascending colon mass.Laparoscopic right hemicolectomy was performed.Pathology revealed poorly differentiated RCC infiltrating the serosa with 4/21 lymph-node metastases.Immunohistochemistry showed AE1/AE3(+),vimentin(+),CDX2(-),CK20(-),and Ki-67(80%+),with retained INI1 expression.Genetic testing indicated KRAS mutation and wild-type BRAFV600E.The patient received no adjuvant therapy and died of peritoneal metastasis within 3 months.Including this case,37 RCC patients(male to female ratio=1.3∶1;mean age 66 years)have been documented.Sixty-two percent of tumors were right-sided.Most exhibited rhabdoid morphology with diffuse vimentin positivity(97.06%)and AE1/AE3 positivity(100.00%),while CDX2 was negative in 85.71%.BRAFV600E mutation was present in 65.00%,and KRAS mutation in 22.73%of tested cases.Among 28 patients with MMR data,60.71%were pMMR and 39.29%dMMR.Although surgery was the primary treatment,78.79%of patients died within 1 year(median survival 6.0 months),with only a few long-term survivors following adjuvant chemotherapy or immunotherapy.Conclusion:RCC is a rapidly progressive colorectal malignancy with extremely poor prognosis and limited response to conventional chemotherapy.Tumor dedifferentiation,INI1 deficiency,and alterations in KRAS/BRAF-MAPK signaling may contribute to its pathogenesis.Surgery remains the mainstay of treatment,but incorporation of immunotherapy,targeted agents,and radiotherapy may offer potential benefits.Further studies are urgently needed to define effective therapeutic strategies.

Paraplegia caused by spinal cord injury is a serious neurological complication, for which surgery is currently the main treatment method. Due to different surgical approaches, patients are usually expected to maintain a passive prone position for a long time or switch between the supine and prone positions. Affected by multiple factors such as neurogenic sensory disorders, pathological changes in muscle tone and operative duration, the risk of intraoperative acquired pressure injury (IAPI) is significantly increased. Current clinical prevention strategies for IAPI in these patients predominantly focus on localized pressure relief during positioning, lacking systematic, standardized comprehensive prevention protocols or evidence-based guidelines. To address it, Department of Nursing, Orthopedics Branch, China International Exchange and Promotive Association for Medical and Health Care, Spinal Trauma Professional Committee, Orthopedics Branch, Chinese Medical Doctor Association, Nursing Group of Spine and Spinal Cord Professional Committee of Chinese Association of Rehabilitation Medicine organized experts in relevant fields to formulate Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury ( version 2025), based on evidence-based medical evidence and latest research results and clinical practice at home and abroad. Eleven recommendations were put forward from the aspects of preoperative risk assessment, intraoperative prevention strategies, postoperative handover and monitoring, and supportive mechanisms for IAPI prevention, aiming to standardize the prevention measures and management strategies of IAPI in paraplegic patients with spinal cord injury and accelerate the recovery of patients and improve the therapeutic effect.

Background and Aims:Rhabdoid carcinoma of the colon(RCC)is an exceptionally rare and highly aggressive malignancy characterized by early metastasis and poor prognosis,with no standardized treatment available.We report a case of ascending colon RCC and summarize previously published cases to improve understanding of its clinicopathologic and molecular features.Methods:The clinical data,imaging,pathology,and immunohistochemistry of one patient treated at Xiangya Hospital were retrospectively analyzed.In addition,36 published RCC cases were systematically reviewed.Clinical characteristics,tumor location,immunophenotype,molecular alterations,treatments,and survival outcomes were extracted and summarized.Results:A 71-year-old man presented with abdominal distension,pain,and altered bowel habits.Imaging and colonoscopy indicated an obstructing ascending colon mass.Laparoscopic right hemicolectomy was performed.Pathology revealed poorly differentiated RCC infiltrating the serosa with 4/21 lymph-node metastases.Immunohistochemistry showed AE1/AE3(+),vimentin(+),CDX2(-),CK20(-),and Ki-67(80%+),with retained INI1 expression.Genetic testing indicated KRAS mutation and wild-type BRAFV600E.The patient received no adjuvant therapy and died of peritoneal metastasis within 3 months.Including this case,37 RCC patients(male to female ratio=1.3∶1;mean age 66 years)have been documented.Sixty-two percent of tumors were right-sided.Most exhibited rhabdoid morphology with diffuse vimentin positivity(97.06%)and AE1/AE3 positivity(100.00%),while CDX2 was negative in 85.71%.BRAFV600E mutation was present in 65.00%,and KRAS mutation in 22.73%of tested cases.Among 28 patients with MMR data,60.71%were pMMR and 39.29%dMMR.Although surgery was the primary treatment,78.79%of patients died within 1 year(median survival 6.0 months),with only a few long-term survivors following adjuvant chemotherapy or immunotherapy.Conclusion:RCC is a rapidly progressive colorectal malignancy with extremely poor prognosis and limited response to conventional chemotherapy.Tumor dedifferentiation,INI1 deficiency,and alterations in KRAS/BRAF-MAPK signaling may contribute to its pathogenesis.Surgery remains the mainstay of treatment,but incorporation of immunotherapy,targeted agents,and radiotherapy may offer potential benefits.Further studies are urgently needed to define effective therapeutic strategies.

Paraplegia caused by spinal cord injury is a serious neurological complication, for which surgery is currently the main treatment method. Due to different surgical approaches, patients are usually expected to maintain a passive prone position for a long time or switch between the supine and prone positions. Affected by multiple factors such as neurogenic sensory disorders, pathological changes in muscle tone and operative duration, the risk of intraoperative acquired pressure injury (IAPI) is significantly increased. Current clinical prevention strategies for IAPI in these patients predominantly focus on localized pressure relief during positioning, lacking systematic, standardized comprehensive prevention protocols or evidence-based guidelines. To address it, Department of Nursing, Orthopedics Branch, China International Exchange and Promotive Association for Medical and Health Care, Spinal Trauma Professional Committee, Orthopedics Branch, Chinese Medical Doctor Association, Nursing Group of Spine and Spinal Cord Professional Committee of Chinese Association of Rehabilitation Medicine organized experts in relevant fields to formulate Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury ( version 2025), based on evidence-based medical evidence and latest research results and clinical practice at home and abroad. Eleven recommendations were put forward from the aspects of preoperative risk assessment, intraoperative prevention strategies, postoperative handover and monitoring, and supportive mechanisms for IAPI prevention, aiming to standardize the prevention measures and management strategies of IAPI in paraplegic patients with spinal cord injury and accelerate the recovery of patients and improve the therapeutic effect.

INTRODUCTION: During the coronavirus disease 2019 (COVID-19) pandemic, multiple guidelines have recommended videolaryngoscope (VL) for tracheal intubation. However, there is no evidence that VL reduces time to tracheal intubation, and this is important for COVID-19 patients with respiratory failure. METHODS: To simulate intubation of COVID-19 patients, we randomly assigned 28 elective surgical patients to be intubated with either McGrath™ MAC VL or direct laryngoscope (DL) by specialist anaesthetists who donned 3M™ Jupiter™ powered air-purifying respirators (PAPR) and N95 masks. The primary outcome was time to intubation. RESULTS: The median time to intubation was 61 s (interquartile range [IQR] 37-63 s) and 41.5 s (IQR 37-56 s) in the VL and DL groups, respectively ( P = 0.35). The closest mean distance between the anaesthetist and patient during intubation was 21.6 ± 4.8 cm and 17.6 ± 5.3 cm in the VL and DL groups, respectively ( P = 0.045). There were no significant differences in the median intubation difficulty scale scores, proportion of successful intubations at the first laryngoscopic attempt and proportion of intubations requiring adjuncts. All the patients underwent successful intubation with no adverse event. CONCLUSION There was no significant difference in the time to intubation of elective surgical patients with either McGrath™ VL or DL by specialist anaesthetists who donned PAPR and N95 masks. The distance between the anaesthetist and patient was significantly greater with VL. When resources are limited or disrupted during a pandemic, DL could be a viable alternative to VL for specialist anaesthetists.
Humans ; COVID-19 ; Intubation, Intratracheal ; Laryngoscopes ; Laryngoscopy ; Respiratory Protective Devices ; Video Recording

Objective To investigate the clinical efficacy and surgical experience of modified posterior fossa decompression combined with dural expansion repair in the treatment of type Ⅰ Chiari malformation complicated with syringomyelia.Methods The clinical data of 47 patients with Chiari type Ⅰ malformation complicated with syringomyelia treated by modified posterior fossa decompression combined with dural expansion repair in our hospital were analyzed retrospectively.The changes of posterior cranial fossa volume,cerebellar tonsil and syringomyelia were evaluated by MRI after operation.The scores of Japanese Orthopaedic Association(JOA)were used to evaluate the improvement of neurological function,and the complications were recorded.Results All the 47 patients successfully completed modified posterior fossa decompression combined with dural expansion repair.The main postoperative complications were unilateral limb numbness,incision pain,fever,subcutaneous effusion and so on,all of which were cured after symptomatic treatment.During the follow-up period,the clinical symptoms and neurological function of the patients were improved in varying degrees,and there was no deterioration of neurological function or death cases.The JOA score of the patients 3 months after operation was(15.83±1.31),which was higher than that of(14.66±2.06)before operation,the difference was statistically significant(P<0.05).MRI showed the extent of syringomyelia was reduced or disap-peared 6 after surgery in all 47 patients.Conclusion Modified posterior fossa decompression combined with dural expansion repair for the treatment of type Ⅰ Chiari malformation complicated with syringomyelia can not only ensure the decompression effect,but also increase the support of the contents of the posterior fossa,effectively prevent postoperative local adhesions,and restore the normal physiological circulation of cerebrospinal fluid in the cisterna magnum,which is an effective treatment method for type Ⅰ Chiari malformation complicated with syringomyelia.

For the treatment of an intertrochanteric fracture combined with femoral head necrosis in middle-age patients, it has been controversial whether to perform fracture reduction and fixation first then total hip replacement, or direct total hip replacement. We present a rare case of 53-year-old male patient suffered from bilateral intertrochanteric fracture caused by a road traffic injury. The patient had a history of femoral head necrosis for eight years, and the Harris score was 30. We performed total hip replacement with prolonged biologic shank prostheses for primary repair. One year after the surgery, nearly full range of motion was achieved without instability (active flexion angle of 110°, extension angle of 20°, adduction angle of 40°, abduction angle of 40°, internal rotation angle of 25°, and external rotation angle of 40°). The Harris score was 85. For the middle-aged patient with unstable intertrochanteric fractures and osteonecrosis of the femoral head, we can choose primary repair for concurrent bilateral intertrochanteric fracture and femoral head necrosis with prolonged shank biologic total hip replacement.
Male ; Middle Aged ; Humans ; Arthroplasty, Replacement, Hip/methods* ; Femur Head/surgery* ; Femur Head Necrosis/surgery* ; Fracture Fixation, Internal/methods* ; Hip Fractures/surgery* ; Biological Products ; Treatment Outcome ; Retrospective Studies

Objective To investigate the effects and mechanisms of TAR DNA-binding protein 43(TDP-43)on oxygen-glucose deprivation(OGD)-induced apoptosis in mouse atrial myocytes(HL-1 cells).Methods The in vitro cultured mouse atrial myocytes(HL-1 cells)were divided into:(1)control group and groups with different OGD treatment times(2,4,8,16 h),and cell viability was detected by CCK-8 assay,and TDP-43 protein expression level was detected by Western blotting,which was used to determine the time point of OGD induction for the subsequent study;(2)control and OGD groups,flow cytometry was used to detect apoptosis,JC-1 staining to detect mitochondrial membrane potential,chemiluminescence to detect adenosine triphosphate(ATP)relative content,microplate method to detect malondialdehyde(MDA)content,and WST-1 method to detect superoxide dismutase(SOD)content.Mouse atrial myocytes(HL-1 cells)transfected with lentivirus were divided into:(1)negative control lentiviral intervention group(NC-shRNA),TDP-43 knockdown lentiviral intervention group(TDP-43-shRNA1,TDP-43-shRNA2,TDP-43-shRNA3),and Western blotting was used to detect the TDP-43 protein expression level,and the group with the highest lentiviral knockdown efficiency was selected as the TDP-43-shRNA for subsequent experiments;(2)NC-shRNA group,TDP-43-shRNA group,OGD+NC-shRNA group,OGD+TDP-43-shRNA group,under normoxic and OGD conditions,flow cytometry was used to detect the apoptosis rate,MitoTracker staining to detect mitochondrial morphology,JC-1 staining to detect mitochondrial membrane potential,chemiluminescence to detect the relative content of ATP,flow cytometry to detect the fluorescence intensity of reactive oxygen species(ROS),microplate to detect the content of MDA,and WST-1 to detect the content of SOD.Results CCK-8 method showed that,with the prolongation of OGD time,the viability of mouse atrial myocytes(HL-1 cells)gradually decreased;Western blotting assay showed that the expression level of TDP-43 protein gradually increased,and both of them showed a strong time-dependence.Compared with control group,mouse atrial myocytes(HL-1 cells)viability was the lowest(P<0.05)and TDP-43 protein expression was the highest(P<0.05)at 16 h of OGD,accordingly,OGD 16 h was chosen as the induction time point for subsequent experiments.Compared with control group,the apoptosis rate,the fluorescence intensity ratio of mitochondrial membrane potential and the content of MDA increased,the relative content of ATP and SOD decreased in OGD group,and the differences were all statistically significant(P<0.05).Western blotting detection showed that compared with NC-shRNA group,the TDP-43-shRNA2 group had the most obvious reduction in TDP-43 protein expression level(P<0.05)and the highest knockdown efficiency,so the TDP-43-shRNA2 group was selected for subsequent experiments.The results of flow cytometry showed that under normoxic conditions,there was no significant change in the apoptosis rate in TDP-43-shRNA group compared with NC-shRNA group(P>0.05);and under OGD conditions,the apoptosis rate in OGD+TDP-43-shRNA group reduced when compared with OGD+NC-shRNA group(P<0.05).MitoTracker staining results showed that the mitochondrial morphology of TDP-43-shRNA group was intact without significant changes compared with NC-shRNA group;the mitochondria of OGD+NC-shRNA group increased in number,most of which were fragmented and scattered in distribution;compared with OGD+NC-shRNA group,the mitochondrial morphology of OGD+TDP-43-shRNA group was restored.Under normoxic conditions,there were no significant changes in mitochondrial membrane potential,relative ATP content,ROS fluorescence intensity,MDA content,and SOD content in TDP-43-shRNA group compared with NC-shRNA group(P>0.05);however,under OGD conditions,the ratio of fluorescence intensity of mitochondrial membrane potential of cells the fluorescence intensity of ROS,and the content of MDA decreased,and the relative content of ATP and the content of SOD increased in OGD+TDP-43-shRNA group compared with that of OGD+NC-shRNA group,and all of these differences was statistically significant(P<0.05).Conclusion TDP-43 exacerbates OGD-induced mitochondrial dysfunction by regulating cardiomyocyte apoptosis;therefore,knockdown of TDP-43 expression is expected to be a potential therapeutic strategy for ischemic cardiomyopathy.

The World Health Organization recommends exclusive breastfeeding up to 6 months and continued breastfeeding for up to 2 years. Breastfeeding mothers adopt different breastfeeding techniques and positions which predispose various musculoskeletal pain. A cross-sectional study was aimed to identify the prevalence of neck and low back pain and its association with various factors (breastfeeding position, feeding side, mode, technique, duration and total breast-feeding sessions per day) among breastfeeding mothers in the Klang Valley. A validated self-administered questionnaire was used to determine the prevalence and associated factors of neck and low back pain. A total of 193 breastfeeding mothers responded to the questionnaire. The prevalence of neck and low back pain among breastfeeding mothers in the Klang Valley was 58% and 69.4%, respectively. There was no significant association between the prevalence of neck and low back pain with various risk factors as the p-values were > 0.05, except for significant association of total breastfeeding sessions per day for neck pain with p = 0.02. Musculoskeletal pain is common among breastfeeding mothers in the Klang Valley, with a higher prevalence of low back pain compared to neck pain.
Breast Feeding